The Renaissance saw significant advances in anatomy and surgical technique. However, despite all this progress, surgery remained a treatment of last resort. Largely because of the associated pain, many patients with surgical disorders chose certain death rather than undergo surgery. Although there has been a great deal of debate as to who deserves the most credit for the discovery of general anesthesia, it is generally agreed that certain scientific discoveries in the late 18th and early 19th centuries were critical to the eventual introduction and development of modern anesthetic techniques.

Two major advances occurred in the late 19th century, which together allowed the transition to modern surgery. An appreciation of the germ theory of disease led rapidly to the development and application of antiseptic techniques in surgery. Antisepsis, which soon gave way to asepsis, reduced the overall morbidity and mortality of surgery to a far more acceptable rate than in previous eras. Concurrent with these developments were the significant advances in pharmacology and physiology which led to the development of general anesthesia and the control of pain.

Opium

The Sumerians are said to have cultivated and harvested the opium poppy (Papaver somniferum) in lower Mesopotamia as early as 3400 BCE,[4][5] though this has been disputed.[6] The most ancient testimony concerning the opium poppy found to date was inscribed in cuneiform script on a small white clay tablet at the end of the third millennium BCE. This tablet was discovered in 1954 during excavations at Nippur, and is currently kept at the University of Pennsylvania Museum of Archaeology and Anthropology. Deciphered by Samuel Noah Kramer and Martin Leve, it is considered to be the most ancient pharmacopoeia in existence.[7][8] Some Sumerian tablets of this era have an ideogram inscribed upon them, "hul gil", which translates to "plant of joy", believed by some authors to refer to opium.[9][10] The term gil is still used for opium in certain parts of the world.[11] The Sumerian goddess Nidaba is often depicted with poppies growing out of her shoulders. About 2225 BCE, the Sumerian territory became a part of the Babylonian empire. Knowledge and use of the opium poppy and its euphoric effects thus passed to the Babylonians, who expanded their empire eastwards to Persia and westwards to Egypt, thereby extending its range to these civilizations.[11] British archaeologist and cuneiformist Reginald Campbell Thompson writes that opium was known to the Assyrians in the 7th century BCE.[12] The term "Arat Pa Pa" occurs in the Assyrian Herbal, a collection of inscribed Assyrian tablets dated to c. 650 BCE. According to Thompson, this term is the Assyrian name for the juice of the poppy and it may be the etymological origin of the Latin "papaver".[9]

The exact composition of mafeisan, similar to all of Hua Tuo's clinical knowledge, was lost when he burned his manuscripts, just before his death.[28] The composition of the anesthetic powder was not mentioned in either the Records of Three Kingdoms or the Book of the Later Han. Because Confucian teachings regarded the body as sacred and surgery was considered a form of body mutilation, surgery was strongly discouraged in ancient China. Because of this, despite Hua Tuo's reported success with general anesthesia, the practice of surgery in ancient China ended with his death.[25]

The name mafeisan combines ma (麻, meaning "cannabis, hemp, numbed or tingling"), fei (沸, meaning "boiling or bubbling"), and san (散, meaning "to break up or scatter", or "medicine in powder form"). Therefore, the word mafeisan probably means something like "cannabis boil powder". Many sinologists and scholars of traditional Chinese medicine have guessed at the composition of Hua Tuo's mafeisan powder, but the exact components still remain unclear. His formula is believed to have contained some combination of:[25][28][29][30]

Others have suggested the potion may have also contained hashish,[26]bhang,[27]shang-luh,[22] or opium.[31]Victor H. Mair wrote that mafei "appears to be a transcription of some Indo-European word related to "morphine"."[32] Some authors believe that Hua Tuo may have discovered surgical analgesia by acupuncture, and that mafeisan either had nothing to do with or was simply an adjunct to his strategy for anesthesia.[33] Many physicians have attempted to re-create the same formulation based on historical records but none have achieved the same clinical efficacy as Hua Tuo's. In any event, Hua Tuo's formula did not appear to be effective for major operations.[32][34]

In 1000, Abu al-Qasim al-Zahrawi (936-1013), an Arab physician who lived in Al-Andalus, published the 30-volume Kitab al-Tasrif, the first illustrated work on surgery. In this book, he wrote about the use of general anesthesia for surgery. c. 1020, Ibn Sīnā (980–1037) described the use of inhaled anesthesia in The Canon of Medicine. The Canon described the "soporific sponge", a sponge imbued with aromatics and narcotics, which was to be placed under a patient's nose during surgical operations.[38]Ibn Zuhr (1091–1161) was another Arab physician from Al-Andalus. In his 12th century medical textbook Al-Taisir, Ibn Zuhr describes the use of general anesthesia. These three physicians were among many who performed operations under inhaled anesthesia with the use of narcotic-soaked sponges.[39][40] Opium made its way from Asia Minor to all parts of Europe between the 10th and 13th centuries.[41]

Throughout 1200 - 1500 A.D. in England, a potion called dwale was used as an anesthetic.[42] This mixture contained bile, opium, lettuce, bryony, and hemlock.[42] Surgeons roused them by rubbing vinegar and salt on their cheekbones.[42] One can find records of dwale in numerous literary sources, including Shakespeare'sHamlet, and the John Keats poem "Ode to a Nightingale".[42] In the 13th century, we have the first prescription of the "spongia soporifica"—a sponge soaked in the juices of unripe mulberry, flax, mandragora leaves, ivy, lettuce seeds, lapathum, and hemlock with hyoscyamus. After treatment and/or storage, the sponge could be heated and the vapors inhaled with anasthetic effect.

AlchemistRamon Llull has been credited with discovering diethyl ether in 1275. [42] Aureolus Theophrastus Bombastus von Hohenheim (1493–1541), better known as Paracelsus, discovered the analgesic properties of diethyl ether around 1525.[43] It was first synthesized in 1540 by Valerius Cordus, who noted some of its medicinal properties. He called it oleum dulce vitrioli, a name that reflects the fact that it is synthesized by distilling a mixture of ethanol and sulfuric acid (known at that time as oil of vitriol). August Sigmund Frobenius gave the name Spiritus Vini Æthereus to the substance in 1730.[44][45]

During the course of his research at the Pneumatic Institution, Davy discovered the anesthetic properties of nitrous oxide.[48] Davy, who coined the term "laughing gas" for nitrous oxide, published his findings the following year in the now-classic treatise, Researches, chemical and philosophical–chiefly concerning nitrous oxide or dephlogisticated nitrous air, and its respiration. Davy was not a physician, and he never administered nitrous oxide during a surgical procedure. He was however the first to document the analgesic effects of nitrous oxide, as well as its potential benefits in relieving pain during surgery:[49]

"As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations in which no great effusion of blood takes place."

19th century

Eastern hemisphere

Hanaoka Seishū (華岡 青洲, 1760–1835) of Osaka was a Japanese surgeon of the Edo period with a knowledge of Chinese herbal medicine, as well as Western surgical techniques he had learned through Rangaku (literally "Dutch learning", and by extension "Western learning"). Beginning in about 1785, Hanaoka embarked on a quest to re-create a compound that would have pharmacologic properties similar to Hua Tuo's mafeisan.[50] After years of research and experimentation, he finally developed a formula which he named tsūsensan (also known as mafutsu-san). Like that of Hua Tuo, this compound was composed of extracts of several different plants, including:[51][52][53]

The reader will note that five of these seven ingredients were thought to be elements of Hua Tuo's anesthetic potion, 1600 years earlier. Some sources claim that Angelica archangelica (often referred to as garden angelica, holy ghost, or wild celery) was also an ingredient.

The active ingredients in tsūsensan are scopolamine, hyoscyamine, atropine, aconitine and angelicotoxin. When consumed in sufficient quantity, tsūsensan produces a state of general anesthesia and skeletal muscleparalysis.[53] Shutei Nakagawa (1773–1850), a close friend of Hanaoka, wrote a small pamphlet titled "Mayaku-ko" ("narcotic powder") in 1796. Although the original manuscript was lost in a fire in 1867, this brochure described the current state of Hanaoka's research on general anesthesia.[54]

Henry Hill Hickman (1800–1830) experimented with the use of carbon dioxide as an anesthetic in the 1820s. He would make the animal insensible, effectively via almost suffocating it with carbon dioxide, then determine the effects of the gas by amputating one of its limbs. In 1824, Hickman submitted the results of his research to the Royal Society in a short treatise titled Letter on suspended animation: with the view of ascertaining its probable utility in surgical operations on human subjects. The response was an 1826 article in The Lancet titled 'Surgical Humbug' that ruthlessly criticised his work. Hickman died four years later at age 30. Though he was unappreciated at the time of his death, his work has since been positively reappraised and he is now recognised as one of the fathers of anesthesia.

By the late 1830s, Humphry Davy's experiments had become widely publicized within academic circles in the northeastern United States. Wandering lecturers would hold public gatherings, referred to as "ether frolics", where members of the audience were encouraged to inhale diethyl ether or nitrous oxide to demonstrate the mind-altering properties of these agents while providing much entertainment to onlookers.[62] Four notable men participated in these events and witnessed the use of ether in this manner. They were William Edward Clarke (1819–1898), Crawford W. Long (1815–1878), Horace Wells (1815–1848), and William T. G. Morton (1819–1868).

While attending undergraduate school in Rochester, New York, in 1839, classmates Clarke and Morton apparently participated in ether frolics with some regularity.[63][64][65][66] In January 1842, by now a medical student at Berkshire Medical College, Clarke administered ether to a Miss Hobbie, while Elijah Pope performed a dental extraction.[64] In so doing, he became the first to administer an inhaled anesthetic to facilitate the performance of a surgical procedure. Clarke apparently thought little of his accomplishment, and chose neither to publish nor to pursue this technique any further. Indeed, this event is not even mentioned in Clarke's biography.[67]

Crawford W. Long was a physician and pharmacist practicing in Jefferson, Georgia in the mid-19th century. During his time as a student at the University of Pennsylvania School of Medicine in the late 1830s, he had observed and probably participated in the ether frolics that had become popular at that time. At these gatherings, Long observed that some participants experienced bumps and bruises, but afterward had no recall of what had happened. He postulated that that diethyl ether produced pharmacologic effects similar to those of nitrous oxide. On 30 March 1842, he administered diethyl ether by inhalation to a man named James Venable, in order to remove a tumor from the man's neck.[68] Long later removed a second tumor from Venable, again under ether anesthesia. He went on to employ ether as a general anesthetic for limb amputations and parturition. Long however did not publish his experience until 1849, thereby denying himself much of the credit he deserved.[68]

On 10 December 1844, Gardner Quincy Colton held a public demonstration of nitrous oxide in Hartford, Connecticut. One of the participants, Samuel A. Cooley, sustained a significant injury to his leg while under the influence of nitrous oxide without noticing the injury. Horace Wells, a Connecticut dentist present in the audience that day, immediately seized upon the significance of this apparent analgesic effect of nitrous oxide. The following day, Wells underwent a painless dental extraction while under the influence of nitrous oxide administered by Colton. Wells then began to administer nitrous oxide to his patients, successfully performing several dental extractions over the next couple of weeks.

William T. G. Morton, another New England dentist, was a former student and then-current business partner of Wells. He was also a former acquaintance and classmate of William Edward Clarke (the two had attended undergraduate school together in Rochester, New York). Morton arranged for Wells to demonstrate his technique for dental extraction under nitrous oxide general anesthesia at Massachusetts General Hospital, in conjunction with the prominent surgeon John Collins Warren. This demonstration, which took place on 20 January 1845, ended in failure when the patient cried out in pain in the middle of the operation.[69]

On 30 September 1846, Morton administered diethyl ether to Eben Frost, a music teacher from Boston, for a dental extraction. Two weeks later, Morton became the first to publicly demonstrate the use of diethyl ether as a general anesthetic at Massachusetts General Hospital, in what is known today as the Ether Dome.[70] On 16 October 1846, John Collins Warren removed a tumor from the neck of a local printer, Edward Gilbert Abbott. Upon completion of the procedure, Warren reportedly quipped, "Gentlemen, this is no humbug." News of this event rapidly traveled around the world.[71]Robert Liston performed the first amputation in December of that year. Morton published his experience soon after.[70]Harvard University professor Charles Thomas Jackson (1805–1880) later claimed that Morton stole his idea;[72] Morton disagreed and a lifelong dispute began.[71] For many years, Morton was credited as being the pioneer of general anesthesia in the Western hemisphere, despite the fact that his demonstration occurred four years after Long's initial experience. Long later petitioned William Crosby Dawson (1798–1856), a United States Senator from Georgia at that time, to support his claim on the floor of the United States Senate as the first to use ether anesthesia.[73]

In 1847, Scottish obstetricianJames Young Simpson (1811–1870) of Edinburgh was the first to use chloroform as a general anesthetic on a human (Robert Mortimer Glover had written on this possibility in 1842 but only used it on dogs). The use of chloroform anesthesia expanded rapidly thereafter in Europe. Chloroform began to replace ether as an anesthetic in the United States at the beginning of the 20th century. It was soon abandoned in favor of ether when its hepatic and cardiactoxicity, especially its tendency to cause potentially fatal cardiac dysrhythmias, became apparent.

In 1880, the Scottish surgeon William Macewen (1848–1924) reported on his use of orotracheal intubation as an alternative to tracheotomy to allow a patient with glottic edema to breathe, as well as in the setting of general anesthesia with chloroform.[78][79][80] All previous observations of the glottis and larynx (including those of Manuel García,[81] Wilhelm Hack[82][83] and Macewen) had been performed under indirect vision (using mirrors) until 23 April 1895, when Alfred Kirstein (1863–1922) of Germany first described direct visualization of the vocal cords. Kirstein performed the first direct laryngoscopy in Berlin, using an esophagoscope he had modified for this purpose; he called this device an autoscope.[84] The death of Emperor Frederick III (1831–1888)[85] may have motivated Kirstein to develop the autoscope.[86]

Until 1913, oral and maxillofacial surgery was performed by mask inhalation anesthesia, topical application of local anesthetics to the mucosa, rectal anesthesia, or intravenous anesthesia. While otherwise effective, these techniques did not protect the airway from obstruction and also exposed patients to the risk of pulmonary aspiration of blood and mucus into the tracheobronchial tree. In 1913, Chevalier Jackson (1865–1958) was the first to report a high rate of success for the use of direct laryngoscopy as a means to intubate the trachea.[88] Jackson introduced a new laryngoscope blade that had a light source at the distal tip, rather than the proximal light source used by Kirstein.[89] This new blade incorporated a component that the operator could slide out to allow room for passage of an endotracheal tube or bronchoscope.[90]

Also in 1913, Henry H. Janeway (1873–1921) published results he had achieved using a laryngoscope he had recently developed.[91] An American anesthesiologist practicing at Bellevue Hospital in New York City, Janeway was of the opinion that direct intratracheal insufflation of volatile anesthetics would provide improved conditions for otolaryngologic surgery. With this in mind, he developed a laryngoscope designed for the sole purpose of tracheal intubation. Similar to Jackson's device, Janeway's instrument incorporated a distal light source. Unique however was the inclusion of batteries within the handle, a central notch in the blade for maintaining the tracheal tube in the midline of the oropharynx during intubation and a slight curve to the distal tip of the blade to help guide the tube through the glottis. The success of this design led to its subsequent use in other types of surgery. Janeway was thus instrumental in popularizing the widespread use of direct laryngoscopy and tracheal intubation in the practice of anesthesiology.[86]

Sodium thiopental, the first intravenous anesthetic, was synthesized in 1934 by Ernest H. Volwiler (1893–1992) and Donalee L. Tabern (1900–1974), working for Abbott Laboratories.[92] It was first used in humans on 8 March 1934 by Ralph M. Waters in an investigation of its properties, which were short-term anesthesia and surprisingly little analgesia. Three months later, John Silas Lundy started a clinical trial of thiopental at the Mayo Clinic at the request of Abbott Laboratories. Volwiler and Tabern were awarded U.S. Patent No. 2,153,729 in 1939 for the discovery of thiopental, and they were inducted into the National Inventors Hall of Fame in 1986.

In 1939, the search for a synthetic substitute for atropine culminated serendipitously in the discovery of meperidine, the first opiate with a structure altogether different from that of morphine.[93] This was followed in 1947 by the widespread introduction of methadone, another structurally unrelated compound with pharmacological properties similar to those of morphine.[94]

After World War I, further advances were made in the field of intratracheal anesthesia. Among these were those made by Sir Ivan Whiteside Magill (1888–1986). Working at the Queen's Hospital for Facial and Jaw Injuries in Sidcup with plastic surgeon Sir Harold Gillies (1882–1960) and anesthetist E. Stanley Rowbotham (1890–1979), Magill developed the technique of awake blind nasotracheal intubation.[95][96][97][98][99][100] Magill devised a new type of angulated forceps (the Magill forceps) that are still used today to facilitate nasotracheal intubation in a manner that is little changed from Magill's original technique.[101] Other devices invented by Magill include the Magill laryngoscope blade,[102] as well as several apparatuses for the administration of volatile anesthetic agents.[103][104][105] The Magill curve of an endotracheal tube is also named for Magill.

The first hospital anesthesia department was established at the Massachusetts General Hospital in 1936, under the leadership of Henry K. Beecher (1904–1976).

Sir Robert Reynolds Macintosh (1897–1989) achieved significant advances in techniques for tracheal intubation when he introduced his new curved laryngoscope blade in 1943.[106] The Macintosh blade remains to this day the most widely used laryngoscope blade for orotracheal intubation.[107] In 1949, Macintosh published a case report describing the novel use of a gum elasticurinary catheter as an endotracheal tube introducer to facilitate difficult tracheal intubation.[108] Inspired by Macintosh's report, P. Hex Venn (who was at that time the anesthetic advisor to the British firm Eschmann Bros. & Walsh, Ltd.) set about developing an endotracheal tube introducer based on this concept. Venn's design was accepted in March 1973, and what became known as the Eschmann endotracheal tube introducer went into production later that year.[109] The material of Venn's design was different from that of a gum elastic bougie in that it had two layers: a core of tube woven from polyester threads and an outer resin layer. This provided more stiffness but maintained the flexibility and the slippery surface. Other differences were the length (the new introducer was 60cm (24in), which is much longer than the gum elastic bougie) and the presence of a 35° curved tip, permitting it to be steered around obstacles.[110][111]

The concept of using a fiberoptic endoscope for tracheal intubation was introduced by Peter Murphy, an English anesthetist, in 1967.[128] By the mid-1980s, the flexible fiberoptic bronchoscope had become an indispensable instrument within the pulmonology and anesthesia communities.[129]

21st century

A modern anaesthetic machine. This particular machine is a "Flow-I" model, manufactured by Maquet

↑ Small, MR (1962). Oliver Wendell Holmes. New York: Twayne Publishers. p.55. ISBN978-0-8084-0237-4. OCLC273508. In a letter to dentist William T. G. Morton, Holmes wrote: "Everybody wants to have a hand in a great discovery. All I will do is to give a hint or two as to names—or the name—to be applied to the state produced and the agent. The state should, I think, be called 'Anaesthesia.' This signifies insensibility—more particularly... to objects of touch."

↑ Thompson RC (July 1926). "The Assyrian herbal: a monograph on the Assyrian vegetable drugs". Isis. 8 (3): 46, 251, 261 and 269. JSTOR223920. Thompson reinforces his view with the following quotation from a cuneiform tablet: 'Early in the morning old women, boys and girls collect the juice, scraping it off the notches (of the poppy-capsule) with a small iron blade, and place it within a clay receptacle.'

1 2 3 Gordon BL (1949). Medicine throughout Antiquity (1 ed.). Philadelphia: F.A. Davis Company. pp.358, 379, 385, 387. OCLC1574261. Retrieved 2010-09-14. Pien Chiao (ca. 300 BCE) used general anesthesia for surgical procedures. It is recorded that he gave two men, named "Lu" and "Chao", a toxic drink which rendered them unconscious for three days, during which time he performed a gastrotomy upon them

↑ Hunke S (1960). Allahs Sonne über dem Abendland: unser arabisches Erbe (in German) (2 ed.). Stuttgart: Deutsche Verlags-Anstalt. pp.279–80. ISBN978-3-596-23543-8. Retrieved 2010-09-13. The science of medicine has gained a great and extremely important discovery and that is the use of general anaesthetics for surgical operations, and how unique, efficient, and merciful for those who tried it the Muslim anaesthetic was. It was quite different from the drinks the Indians, Romans and Greeks were forcing their patients to have for relief of pain. There had been some allegations to credit this discovery to an Italian or to an Alexandrian, but the truth is and history proves that, the art of using the anaesthetic sponge is a pure Muslim technique, which was not known before. The sponge used to be dipped and left in a mixture prepared from cannabis, opium, hyoscyamus and a plant called Zoan.

↑ Kritikos PG, Papadaki SP (1967). "The History of the Poppy and of Opium and Their Expansion in Antiquity in the Eastern Mediterranean Area". Bulletin on Narcotics. 19 (4): 5–10. ISSN0007-523X.

↑ Bain, JA; Spoerel, WE (November 1964). "Observation on the use of cuffed tracheostomy tubes (with particular reference to the James tube)". Canadian Journal of Anesthesia. 11 (6): 598–608. doi:10.1007/BF03004104. PMID14232175.

↑ Janeway, HH (November 1913). "Intra-tracheal anesthesia from the standpoint of the nose, throat and oral surgeon with a description of a new instrument for catheterizing the trachea". The Laryngoscope. 23 (11): 1082–90. doi:10.1288/00005537-191311000-00009.

Matsuki, A (2006). "Why did Hanaoka's Method of Anesthesia Decay Rapidly at the End of the Edo Period?". Nihon Ishigaku Zasshi (Journal of the Japanese Society for Medical History) (in Japanese). 52 (1): 40–1. ISSN0549-3323.